G protein nucleolar 3 (GNL3), a nucleolar GTP-binding protein, is highly expressed in progenitor cells, stem cells, and various types of cancer cells. Therefore, it is considered to have an important role in cancer pathogenesis. GNL3 has been reported to play crucial roles in cell proliferation, cell cycle regulation, inhibition of differentiation, ribosome biogenesis, and the maintenance of stemness, genome stability and telomere integrity. Furthermore, GNL3 has recently been shown to be involved in cancer invasion and metastasis. However, the biological significance of GNL3 in the invasion and metastasis of colon cancer remains unclear. This study was performed to address this gap in knowledge. GNL3 expression was upregulated in colon cancer tissue specimens and correlated with tumor differentiation, invasion and metastasis. GNL3 overexpression promoted cell proliferation, invasion, migration and the epithelial-mesenchymal transition (EMT) in colon cancer cells. Moreover, inhibition of the EMT and the Wnt/β‑catenin signaling pathway induced by GNL3 knockdown was partially reversed by lithium chloride (LiCl). Based on these data, GNL3 promotes the EMT in colon cancer by activating the Wnt/β‑catenin signaling pathway. In summary, GNL3 is upregulated in colon cancer and plays an important role in tumor growth, invasion and metastasis. Strategies targeting GNL3 are potential treatments for colon cancer.

Lysyl oxidase‑like 2 (LOXL2), a member of the lysyl oxidase gene family, is involved in the progression of hepatocellular carcinoma progression and metastasis. Increased expression of LOXL2 has been identified in several types of cancer, including hepatocellular carcinoma. Recently, LOXL2 has been reported to promote epithelial‑mesenchymal transition by reducing E‑cadherin expression via the upregulation of Snail expression. The present study provided evidence demonstrating that LOXL2 inhibited the expression of fructose‑1, 6‑biphosphatase (FBP1) and enhanced the glycolysis of Huh7 and Hep3B hepatocellular carcinoma cell lines in a Snail‑dependent manner. Overexpression of the point‑mutated form of LOXL2 [LOXL2(Y689F)], which lacks enzymatic activity, does not affect the expression of Snail1 or FBP1. Notably, targeting extracellular LOXL2 of Huh7 cells with a therapeutic antibody was unable to abolish its regulation on the expression of Snail and FBP1. Knockdown of LOXL2 also interrupted the angiogenesis of Huh7 and Hep3B cells, and this effect could be rescued by the overexpression of Snail. Furthermore, upregulation of hypoxia‑inducible factor 1α (HIF‑1α) and vascular endothelial growth factor (VEGF) expression was observed in Huh7 and Hep3B cells expressing wild‑type LOXL2. Notably, the selective LOXL2 inhibitor LOXL2‑IN‑1 could upregulate the expression of FBP1 and inhibit the expression of Snail, HIF‑1α and VEGF in HCC cells, but not in FBP1‑knockdown cells. The results of the present study indicated that the intracellular activity of LOXL2 upregulated HIF‑1α/VEGF signaling pathways via the Snail‑FBP1 axis, and this phenomenon could be inhibited by LOXL2 inhibition. Collectively, these findings further support that LOXL2 exhibits an important role in the progression of hepatocellular carcinoma and implicates LOXL2 as a potential therapeutic agent for the treatment of this disease.